Patent IL-107085-A (IL)
Title: Substituted pyrimidines and pharmaceutical compositions for inhibiting sorbitol dehydrogenase comprising the same
IPC: A61P3/08
Filed: 1993-09-23
Abstract: A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of a sorbitol dehydrogenase inhibitor of the formula (I) wherein R1 is hydrogen, CF3, (C1-C6) alkyl-S-(C1-C6) alkyl, (C1-C6) alkyl-SO- (C1-C6) alkyl, (C1-C6) alkyl-SO2-(C1-C6) alkyl, hydroxy- (C1-C6)alkyl, dihydroxy-(C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6)alkoxycarbonyl -(C1-C6) alkyl, 7 ט" ז בטבת התשס" א - January 11, 2001 aryl-(C1-C6) alkyl, (C1-C6)alkoxycarbonylaryl, aryl- (C1-C6) alkyloxy wherein the aryl moeity is selected from phenyl and naphthyl, heteroaryl selected from pyridyl, furyl, tetrahydrofuryl, thienyl, imidazolyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, benzothiazolyl, benzofuranyl, and benzothienyl; heteroaryl- (C1-C6) alkyl heteroaryl - (C1-C6) alkyloxy and wherein said heteroaryl group, the aryl moieties of said aryl - (C1-C6) alkyl, (C1-C6) alkoxycarbonylaryl and aryl - (C1-C6) alkyloxy and the heteroaryl moeity of said heteroaryl - (C1-C6) alkyl may optionally be substituted with one or more substituents independently selected from chloro, bromo, (C1-C6) alkyl, (C1-C6) alkoxy, -S(C1-C6) alkyl, -SO-(C1-C6) alkyl, -SO2-(C1-C6) alkyl, hydroxy - (C1-C6) alkyl and trifluoromethyl; or R1 is a group of the formula wherein the dotted line represents an optional double bond, W, Q and Z are independently selected from hydrogen, (C1-C6) alkyl and trifluoromethyl, phenyl, furyl, triazolyl, thiazolyl and thienyl, wherein said phenyl, furyl, triazolyl, thiazolyl and thienyl may optionally be substituted with one or more substituents independently selected from (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl and hydroxy; or R1 is a group of the formula -C(O)R6, wherein R6 is hydrogen, (C1-C6) alkyl, aryl selected from phenyl and naphthyl, or heteroaryl selected from pyridyl, furyl, thienyl, imidazolyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, benzothiazolyl, benzofuranyl and benzothienyl, wherein said aryl and heteroaryl groups may optionally be substituted with one or more substituents independently selected from chloro, bromo, nitro, trifluoromethyl, (C1-C6) alkoxy, -S-(C1-C6) alkyl, -SO-(C1-C6) alkyl and -SO2-(C1-C6) alkyl; or R1 is a group of the formula wherein R7 is aryl selected from phenyl and naphthyl, or heteroaryl selected from pyridyl, furyl, thienyl, imidazolyl, pyrazolyl, triazolyl, thiazolyl, oxazolyl, benzothiazolyl, benzofuranyl, benzothienyl and quinolyl, wherein said aryl and heteroaryl groups may optionally be substituted with one or more substituents, preferably with from zero to two substituents, independently selected from chloro, bromo, (C1-C6) alkyl, (C1-C6) alkoxy, -S- (C1-C6) alkyl, -SO-(C1-C6) alkyl, -SO2-(C1-C6) alkyl and trifluoromethyl, and Y is hydrogen, benzyl, 8 ט" ז בטבת התשס" א - January 11, 2001 acetyl, benzoyl, aryl selected from phenyl and naphthyl, heteroaryl selected from furyl, thienyl, thiazolyl and oxazolyl, wherein said aryl and heteroaryl groups may optionally be substituted with one or more substituents independently selected from chloro, bromo, nitro, trifluoromethyl, (C1-C6) alkyl, (C1-C6) alkoxy, -S-(C1-C6) alkyl, -SO-(C1-C6) alkyl, and -SO2-(C1-C6) alkyl; R2 and R3 are defined in the specification, R4 is hydrogen, chloro, bromo, cyano, nitro, trifluoromethyl, amino, (C1-C6) alkyl, (C1-C6) hydroxyalkyl, (C1-C6) alkoxy, phenyl, naphthyl or furyl, wherein said phenyl, naphthyl and furyl may optionally be substituted with one or more substituents independently selected from chloro, bromo, trifluoromethyl, (C1-C6) alkyl, (C1-C6) alkoxy, -S-(C1-C6) alkyl, -SO-(C1-C6) alkyl, -SO2-(C1-C6) alkyl and hydroxy; and R5 is hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, trifluoromethyl, (C1-C6) hydroxyalkyl, -S-(C1-C6) alkyl, -SO-(C1-C6) alkyl, -SO2-(C1-C6) alkyl, phenyl or furyl, wherein said phenyl and furyl may optionally be substituted with one or more substituents independently selected from chloro, bromo, trifluoromethyl, (C1-C6) alkyl, (C1-C